Chitosan/PAMAM/Hydroxyapatite Engineered Drug Release Hydrogels with Tunable Rheological Properties.

Alessandro Pistone,Roberto Romeo,Annamaria Visco,Consuelo Celesti,Daniela Iannazzo,Salvatore V Giofré,Cristina Scolaro

doi:10.3390/polym12040754

Alessandro Pistone, Roberto Romeo + Show 5 more

Open Access

https://doi.org/10.3390/polym12040754

Copy DOI

Journal: Polymers	Publication Date: Mar 31, 2020
Citations: 21	License type: CC BY 4.0

Affiliation: University of Messina

Abstract

In this paper, a new formulation of biodegradable and bioresorbable chitosan-based hydrogel for controlled drug release was investigated. A chitosan–dendrimer–hydroxyapatite hydrogel, obtained by covalently grafting chitosan powder with an hyperbranched PAMAM dendrimer followed by in-situ precipitation of hydroxyapatite and gelification, was synthesized and characterized by FTIR, NMR, TGA, XRD and rheological studies. The hydrogels have been also doped with an anti-inflammatory drug (ketoprofen) in order to investigate their drug release properties. Chemical and chemical-physical characterizations confirmed the successful covalent functionalization of chitosan with PAMAM and the synthesis of nanostructured hydroxyapatite. The developed hydrogel made it possible to obtain an innovative system with tunable rheological and drug-releasing properties relative to the well-known formulation containing chitosan and hydroxyapatite powder. The developed hydrogel showed different rheological and drug-releasing properties of chitosan matrix mixed with hydroxyapatite as a function of dendrimer molecular weight; therefore, the chitosan–dendrimer–hydroxyapatite hydrogel can couple the well-known osteoconductive properties of hydroxyapatite with the drug-release behavior and good processability of chitosan–dendrimer hydrogels, opening new approaches in the field of tissue engineering based on biopolymeric scaffolds.

Highlights

The development of biomaterials for application in medicine represents a fascinating challenge in the field of materials science
On the basis of these considerations, we developed a new formulation for soft tissue engineering applications and for controlled drug release, constituted by a chitosan–dendrimer–hydroxyapatite hydrogel obtained by covalently grafting chitosan powder with hyperbranched PAMAM dendrimers with different molecular weights followed by in-situ precipitation of hydroxyapatite and gelification; in such a manner, the coupling of dendrimeric structure and hydroxyapatite together inside the chitosan matrix made it possible to obtain an innovative system with tunable rheological and drug-releasing properties relative to the well-known formulation containing chitosan and hydroxyapatite powder
Chitosan chains functionalized with poly(amidoamine) (PAMAM) dendrimers were synthesized starting from PAMAM-CO2 Me dendrimer of generation 1.5, 2.5 and 3.5 which were produced as reported in literature by the repetition of two processes: (a) Michael addition of methyl acrylate (MA)

Summary

Introduction

The development of biomaterials for application in medicine represents a fascinating challenge in the field of materials science. Among the different 3D biopolymeric scaffolds, polysaccharide-based hydrogels composed of chitosan, alginate, dextran or hyaluronic acid have been widely investigated for bone and soft tissue engineering applications, owing to their high biocompatibility and biodegradability, low cost, ease of handling, viscoelastic properties comparable to soft tissues, possibility of gelation in situ, and ability to provide an ideal hydrated environment for the growth of cells or tissues [10]. Based on their chemistry, they can be cross-linked, allowing the incorporation of cells, growth factors and the controlled release of bioactive molecules [11].

Methods

Results

Conclusion